Retromer directs membrane protein trafficking within the endosome. The exposure of proteins to the extracellular environment is dependent on how the travel through the various regions of the cell. The work will lead to a richer understanding of how this process is regulated by protein complexes. These complexes act within cells to drive the formation of membrane transport tubules containing cargo molecules.
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less
The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human ....The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human neurodegenerative diseases. This project plans to use a combination of cutting-edge X-ray crystallographic and electron microscopy approaches to develop a multi-scale, pseudo-atomic structure of retromer and key regulatory proteins to understand how this multi-component protein machinery is assembled to control intracellular transport.Read moreRead less
Regulation of human immunodeficiency virus type 1 (HIV-1) replication by viral and cellular proteins. Using a mouse model, human cells will be treated with a very powerful antiviral protein using a gene therapy approach so as to block the human immunodeficiency virus (HIV) from growing. By learning how this antiviral protein works, this project will assist in the development of new strategies to treat HIV infection.
Structural analysis of a novel plasma membrane coat complex. The plasma membrane of mammalian cells forms a crucial barrier between the cell and the outside world. This project investigates how a newly-discovered family of proteins work together to generate specialised regions of the plasma membrane called caveolae.
Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat prote ....Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat proteins called cavins have recently been discovered. Cavins are essential for the formation of caveolae, and this project seeks to understand how these multiprotein complexes are assembled at the membrane interface and control caveola function at the molecular level.Read moreRead less
Defining the molecular mechanisms of intracellular protein trafficking. Intracellular trafficking of proteins is critical for normal cell function and defects can lead to many different human diseases. Outcomes from this project will lead to insights into how trafficking is regulated at the atomic level and will help place Australia at the forefront of international efforts to understand this essential process.
Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.